Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders (BPA/Benzoate)

Baylor College of Medicine

Status: Completed

Conditions: Urea Cycle Disorders, Inborn

Treatments: Drug: Sodium Benzoate; Drug: Sodium Phenylbutyrate

Study type: Interventional

Funder types: Other

Identifiers

NCT02111200

H-33157

Details and patient eligibility

About

The investigators will study and compare how effectively sodium phenylbutyrate, sodium benzoate, and a combination of the two, help excrete nitrogen in healthy volunteers. Subject participation will require three, separate, four-day study periods at least one week apart. During one study period (also called a treatment arm), subjects will take sodium phenylbutyrate; during another they will take sodium benzoate; during another they will take a combination of the two medications.

We expect to find that phenylbutyrate is more effective at removing nitrogen than benzoate or a combination of the two.

Enrollment: 7 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy volunteers

Exclusion criteria

• Subjects with (a) a history of frequent dietary protein intolerance, (b) a history of chronic or acute liver diseases which may result in altered hepatic synthetic capacity (e.g., hepatitis), (c) acute or chronic disease or on medications that in the opinion of the clinical investigators will interfere with the measurements (e.g., drugs which may have hepatotoxicity as potential side effects), (d) a physical disability that will interfere with their ability to either conform to the dietary regimes or undergo the isotopic infusions, (e) pregnancy or recent (<6 months)/current lactation, (f) intercurrent evidence of significant hyperammonemia (more than 100 µmol/L), (g) any clinical abnormality of Grade 3 or greater according to the Common Terminology Criteria for Adverse Events v.4.0 (CTCAE), (h) any condition(s) not covered by the CTCAE, or (i) a severe or life-threatening toxicity at screening, will be excluded from the study. Subjects taking ammonia scavenger medications will not be enrolled.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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7 participants in 3 patient groups

Sodium Benzoate arm

Active Comparator group

Description:

Sodium benzoate 5.5 g/m2/day divided into three equal doses per day (maximum dose 12 g/day) for 3 days

Treatment:

Drug: Sodium Benzoate

Sodium Phenylbutyrate arm

Active Comparator group

Description:

Sodium phenylbutyrate 7.15 g/m2/day divided into three equal doses per day (maximum dose of 20 g/day) for 3 days

Treatment:

Drug: Sodium Phenylbutyrate

Mix Arm

Active Comparator group

Description:

Sodium Phenylbutyrate 3.575 g/m2/day and Sodium Benzoate 2.75 g/m2/day will be given in three equal doses per day for 3 days

Treatment:

Drug: Sodium Benzoate

Drug: Sodium Phenylbutyrate